Alzheimer's disease: we will go the other way!
Claudio Torres from Drexel University in Pennsylvania, Philadelphia wondered whether physiological aging (loss of the ability to divide) of brain cells could be the cause of inflammation developing in Alzheimer's disease.
By themselves, neurons practically do not divide, but active division is characteristic of other brain cells – stellate cells, astrocytes. The function of these cells, which make up about 80-90% of brain tissue, is to ensure the vital activity of neurons, including the removal of plaques of the beta-amyloid protein associated with Alzheimer's disease.
Torres and his colleagues exposed astrocytes to hydrogen peroxide, a compound that triggers a metabolic stress mechanism similar to that observed in normal aging. As scientists expected, the cells stopped dividing and began to express genes characteristic of the phase of physiological aging. Moreover, they began to release a huge amount of inflammatory proteins.
After that, the researchers analyzed the content of cells in the phase of physiological aging in sections of the brain tissue of embryos, people aged 35-50 years and people aged 78-90 years. Healthy brain tissue of people over the age of 35 years contained 6-8 times more cells in the phase of physiological aging than the tissue of embryos. Moreover, the brains of adults with Alzheimer's disease contained more of these cells than the brains of their peers who did not have this diagnosis. In the brain tissue samples of the oldest people, about 30% of astrocytes showed signs of physiological aging, and people with Alzheimer's disease had 10% more such cells.
To identify the relationship between physiological aging and amyloid plaques, scientists placed beta-amyloid in dies filled with astrocytes. After a while, they demonstrated that the cells around the clusters of beta-amyloid began to age rapidly.
Torres believes that amyloid plaques and aging astrocytes fall into a vicious circle – as the body ages, the ability of astrocytes to eliminate amyloid plaques weakens, the accumulation of which, in turn, accelerates their physiological aging.
What can be done to break this circle? Currently, Torres and his group are trying to figure out whether delaying physiological aging can prevent the development of Alzheimer's disease.
Preventing physiological aging can do a disservice, as it is fraught with an increased risk of cell malignancy. An alternative option is to eliminate aged cells. This approach was already proposed last year by James Kirkland from the Mayo Clinic (Clearance of p16INK4a-positive senescent cells delays aging-associated disorders).
Another possible option is blocking the secretion of inflammatory compounds by aged cells. Specialists working under the guidance of Judith Campisi from the Institute for the Study of Aging. Baka in Novato, California has already taken the first step in this direction. They identified a compound that suppresses the destructive secretion. They are currently working on improving the effectiveness of the method.
According to Torres, after 50 years of unsuccessful search for a cure for Alzheimer's disease, the new data looks very encouraging.
The bitter truth is that the fight against the main symptom of Alzheimer's disease – amyloid plaques – is useless. Last month, information was made public about the failure of two major clinical trials that evaluated the effectiveness of methods of exposure to beta-amyloid plaques. Moreover, in the period from 1998 to 2011, 101 experimental methods of treating Alzheimer's disease were forgotten and only 3 drugs are approaching the pharmaceutical market. /APPROX
Currently, several clinical studies are being conducted on methods aimed at protecting synapses – axon contact zones through which neurons transmit information to each other.
The third hope is the work being conducted under the direction of Gary Landreth from the University of the Western Reserve District in Cleveland, Ohio. This work is devoted to the antitumor drug bexarotine, which eliminates half of the amyloid plaques in the brain of mice within three days with simultaneous rapid recovery of their cognitive abilities. Landreth warns against extrapolating the results to humans, but is currently studying its effect on people without Alzheimer's disease.
Article by Rekha Bhat et al. Astrocyte Senescence as a Component of Alzheimer's Disease is published in the journal PLoS ONE.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to NewScientist: Aging cells offer new target for Alzheimer's therapy?11.10.2012